The present disclosure relates generally to fusion proteins for treating Giant Axonal Neuropathy (GAN). More particularly, the present disclosure is directed to fusion proteins including gigaxonin coupled to at least one cell penetrant peptide.
Giant Axonal Neuropathy (GAN) is an autosomal recessive disorder of the nervous system characterized by cytoskeletal disorganization. Patients suffering from GAN experience both peripheral and central nervous system manifestations including progressive polyneuropathy, ataxia, and seizures. Generally, these patients become bedridden early in life, and are not expected to live past the third decade of life.
The GAN gene encodes for gigaxonin, a 68 kDa protein which directs ubiquitin mediated proteolysis of cytoskeletal components. In the absence of gigaxonin, these proteins form cytoskeletal aggregates which result in distended and dysfunctional axons, particularly neuronal axons. This aggregate phenotype can be observed in other cells types, and aggregates of vimentin in fibroblasts have been defined in previous work to serve as a phenotypic marker for the disease state.
Because GAN is a single gene mutation disorder, it is a viable candidate for protein replacement therapeutics. Accordingly, there is a need in the art for treating GAN.